VA Cooperative Studies Program Trial 578 ContrastAssociated Acute Kidney Injury CAAKI Common post angiography amp associated with death dialysis progressive CKD Potentially preventable ID: 935921
Download Presentation The PPT/PDF document "Prevention of Serious Adverse Events Fol..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Prevention of Serious Adverse Events Following Angiography (PRESERVE) Trial
VA Cooperative Studies Program Trial # 578
Slide2Contrast-Associated Acute Kidney Injury (CA-AKI)
Common
post-
angiography & associated with death, dialysis, progressive CKD
Potentially preventable known timing of renal insult
Many trials of
NaCl
vs. NaHCO
3 and of NAC vs. placeboUnderpowered with divergent findingsMeta-analyses inconclusivePersistent equipoise on efficacy of NaHCO3 and NAC despite widespread utilization in clinical practice
Slide3PRESERVE trial – hypotheses, design, and endpoints
Compared with isotonic IV
NaCl
, isotonic IV NaHCO
3 ↓ serious adverse outcomes following angiography
Compared with placebo, oral NAC ↓ serious adverse outcomes following angiography
Beneficial effect mediated by ↓ in CA-AKI
2 x 2 factorial design
10 endpoint – death, dialysis, or persistent ↑ SCr ≥ 50% @ 90 days 20
endpoints
– CA-AKI (↑
SCr
≥ 0.5 mg/dL or ≥25% @ 4 days); individual components of 10 endpoint; hospitalization for HF, stroke, ACS; all-cause hospitalization Analyses – logistic regression
Slide4PRESERVE trial –
pt
population
Pts undergoing coronary or non-coronary angiographyBaseline
eGFR 45-60 mL/min + DM or
15-45 mL/min ± DM
Key exclusions – emergent angiography, ongoing AKI, decompensated HF
Sample size target – 7,680 pts
90% power, p=0.025, relative 25% ↓ 10 endpoint for each intervention from 8.7% to 6.5%, 3% loss to f/u53 sites in US, Australia, NZ, Malaysia
Slide5PRESERVE trial – study interventions
IV fluids
Pre-
angio
1-3 mL/kg/hr over 1-12
hrs
total volume 3-12 mL/kgIntra-angio 1-1.5 mL/kg/hrPost-angio 1-3 mL/kg/hr over 2-12 hrs
total volume 6-12 mL/kg
Local providers specified rate, duration, volume w/i these parameters
NAC/placebo capsules1200 mg po bid x 5 days starting ~ 1
hr
prior to angiography
Slide6Trial stopped after 5,177 pts (67%) randomized @ pre-planned
interim analysis based on:
- results to date
- conditional power <12% with full enrollment
- 4,993 pts in analytic cohort
- NaHCO
3
*NAC interaction p=0.33
Slide7Pt/
angio
characteristics & study intervention comparisons
Slide8Pt/
angio
characteristics & study intervention comparisons
No differences across
groups
Slide9Primary and secondary endpoint comparisons – NaHCO
3
vs.
NaCl
Slide10Pre-specified sub-groups – 1
0
endpoint and CA-AKI - NaHCO3 vs.
NaCl
Slide11Pre-specified sub-groups – 1
0
endpoint and CA-AKI - NaHCO3 vs.
NaCl
No significant differences considering multiple comparisons
Slide12Primary and secondary endpoint comparisons – NAC vs. placebo
Slide13Pre-specified sub-groups – 1
0
endpoint and CA-AKI – NAC vs. placebo
Slide14Pre-specified sub-groups – 1
0
endpoint and CA-AKI – NAC vs. placebo
No significant differences considering multiple comparisons
Slide15PRESERVE trial - summary
IV NaHCo
3
is not more effective
than IV NaCl for prevention of serious outcomes or AKI following angiography
NAC is
not effective
for prevention of serious outcomes or AKI following angiography
Current standard of care for prevention of CA-AKI and associated adverse outcomes should be:IV isotonic NaClNo use of NAC
Slide16PRESERVE trial sites